Nitric oxide reaction with lipid peroxyl radicals spares α-tocopherol during lipid peroxidation. Greater oxidant protection from the pair nitric oxide/α-tocopherol than α-tocopherol/ascorbate

Academic Article


  • The reactions of nitric oxide (·NO) and α-tocopherol (α-TH) during membrane lipid oxidation were examined and compared with the pair α- TH/ascorbate. Nitric oxide serves as a more potent inhibitor of lipid peroxidation propagation reactions than α-TH and protects α-TH from oxidation. Mass spectrometry, oxygen and ·NO consumption, conjugated diene analyses, and α-TH fluorescence determinations all demonstrated that ·NO preferentially reacts with lipid radical species, with α-TH consumption not occurring until ·NO concentrations fell below a critical level. In addition, α-TH and ·NO cooperatively inhibit lipid peroxidation, exhibiting greater antioxidant capacity than the pair α-TH/ascorbate. Pulse radiolysis analysis showed no direct reaction between ·NO and α-tocopheroxyl radical (α-T·), inferring that peroxyl radical termination reactions are the principal lipid- protective mechanism mediated by ·NO. These observations support the concept that ·NO is a potent chain breaking antioxidant toward peroxidizing lipids, due to facile radical-radical termination reactions with lipid radical species, thus preventing α-TH loss. The reduction of α-T by ascorbate was a comparatively less efficient mechanism for preserving α-TH than ·NO- mediated termination of peroxyl radicals, due to slower reaction kinetics and limited transfer of reducing equivalents from the aqueous phase. Thus, the high lipid/water partition coefficient of ·NO, its capacity to diffuse and concentrate in lipophilic milieu, and a potent reactivity toward lipid radical species reveal how ·NO can play a critical role in regulating membrane and lipoprotein lipid oxidation reactions.
  • Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 18211081
  • Author List

  • Rubbo H; Radi R; Anselmi D; Kirk M; Barnes S; Butler J; Eiserich JP; Freeman BA
  • Start Page

  • 10812
  • End Page

  • 10818
  • Volume

  • 275
  • Issue

  • 15